1. Field of the Invention
The present invention relates to a device which is based on centrifugal force for achieving more effective pulverization of a powdered inhalation medicament in a manner that the penetration of medicament into the lungs is improved and the adhesion to the upper respiratory passages is reduced for alleviating the side effects caused thereby.
2. Description of the Related Art
It is generally known that the size of medicament particles should be 1-5 microns, preferably 2-3 microns, for the best possible penetration into their destination, i.e. deep into the lungs. The most common metering device is a so-called inhalation aerosol which is quite readily capable of reaching the optimal particle size. In addition to inhalation aerosols, an increasing number of powder inhalators are presently in use as these offer certain benefits, e.g. there is no need for ozone-destroying propellants. Several clinical studies have indicated that, with the same amount of medicament, the powder inhalators do not achieve the same effect as inhalation aerosols but it takes up to 2-3 times larger dosages to get the same results. The reason for this is considered to be the fact that a powdered medicament issuing from powder inhalators has too large a particle size. Thus, most of the medicine dosage coming out of inhalators is retained in upper respiratory passages which, with certain medicines, can cause serious side effects. The medicine dosages required for different inhalation medicaments vary considerably, the smallest being appr. 0.01 mg and the largest 20 mg. When small amounts of medicine are metered in powdered form, it is generally necessary to use some adjuvant or carrier, so that the sufficiently precise measuring of a dosage would be possible with the present technology. No matter if the dosage comprises just medicine or has a carrier admixed therein, the medicine dosage substantially comprises inter-adhered particles and most of these agglomerates are too large to penetrate into the lungs. As the agglomerates are released in a powder inhalator into an air flow passing into the lungs of a patient, there will occur some dispersal of these particle deposits, said dispersal resulting from the formulation of a powdered medicament and the construction of an inhalator. It is known that constructions creating a strong turbulence are capable of more effective pulverization.
In practice, however, no prior known powder inhalator structure and/or medicine formulation has produced results that would be equal to those achieved by an ordinary inhalation aerosol. It has been suggested as a partial solution that inhalation should be effected with as much force as possible, whereby the turbulence and pulverization of particles would accordingly be most effective. However, a quick inhalation is difficult for a person suffering e.g. from serious asthma and, on the other hand, a quick inhalation increases the residue in upper respiratory tracts. According to studies, pulverization of agglomerates is indeed intensified but the overall benefit is marginal. The best pulmonary penetration in relation to the adherence of medicament to upper respiratory tracts has been achieved by slow inhalation, corresponding to a flow rate of appr. 30 l/min or 0.5 1/sec.
The only prior known powder inhalator is the device described in Finnish Patent application No. 871000 which has been designed in an effort to produce a clearly defined turbulence for pulverizing agglomerations of medicine. The centrally directed deflectors inside the device or the helical chute are described as setting the air flow in a spinning motion, whereby the medicine particles entrapped in the air abrade as a result of centrifugal force against the walls of the structure as well as collide into each other with resulting pulverization. The device described in the cited application is a TURBUHALER.RTM. inhalator device marketed by Draco from Sweden. The pulverizing structure of the TURBUHALER.RTM. device is a helical chute or groove. Laboratory tests indicated that this device had a relatively good pulverization of agglomerates of medicine which could be greatly improved upon by means of a device of the present invention. In view of the pulverization of agglomerates or accumulations of medicine, there are a few defects. in the device. The helical groove has in the centre thereof an open space having less air resistance than inside the groove. Accordingly, the flow rate of air and centrifugal force on the circumference of the groove are less than theoretical. Since the particles advance in the groove under a force caused by air resistance and centrifugal force tends to push the particles perpendicularly to the circumferential tangent, the actual force applied to the particles is a resultant of these forces and is applied diagonally relative to the circumferential tangent. Thus, the centrifugal force resulting from the spinning motion cannot be utilized to its full extent for the pulverization of accumulations. In all deflector structures according to the cited application, the particles escape from the device within a few thousandths of a second when using conventional inhalation rates of 30-60 l/min and that is a very short time for an effective pulverization. The residence time can be lengthened, e.g., by increasing the number of helices in groove portions or the number of separate deflector structures or the length of zigzagging air flow channels, but this would complicate manufacturing and cleaning and medicine residues in the actual device would increase. After all, cleaning of the structures disclosed in the cited application is difficult as it is.
The European Patent application No. 215559 discloses a powder inhalator, wherein one or more balls travel as a result of air flow around a periphery which is substantially circular in configuration. The air flow comes into contact with the periphery tangentially relative thereto. The medicine is adhered either to the surface of balls or to the surface of the circulation periphery from which it is removed and is pulverized by the action of the rolling balls. The device employs a centrifugal force for fractionating loose particles in a manner that the discharge of air occurs centrally relative to the circulating path. Thus, the pulverization of medicine is a result of a mechanical contact between the balls and the surface.
In the cited structure, the balls close the circulating path for the most part and, thus, there cannot be high speeds of circulation for the balls or medicine particles and, hence, there cannot be major centrifugal forces. It is obviously difficult to use the device for repeatedly metering out exact doses of medicine. The British Patent No. 1485163 describes a device, wherein a powdered medicament containing elongated capsule provided with pierced ends is set through the action of inhalation air in a rotating motion inside a cylindrical mixing chamber. Piercing of the capsule is effected in a capsule-shaped space which is in open communication with the mixing chamber and the capsule is jerked therefrom along with the air flow into the mixing chamber to spin around its vertical axis. The medicament flings through the ends of the capsule into the mixing chamber and further into an inhalation channel. The device according to this Patent is an INALATORE.RTM. I.S.F. inhalator device. Laboratory tests showed that the device had a reasonable pulverizing effect for accumulations of medicine but a distinctly poorer effect than what is achieved by a device of the present invention.
The device disclosed in the cited Patent would have an improved pulverizing effect if the rotating speed of a capsule and air in the mixing chamber could be increased by using the centrifugal force more effectively for pulverization. This is impossible with the cited structure since it is prevented by the own mass of a capsule and by the friction resulting from its rotation. In addition, the space in communication with the mixing chamber and intended for piercing the capsule is asymmetrical relative to the rotating direction and produces a decelerating turbulence.
British Patent No. 1331216 discloses a device operating on the capsule discharging mechanism, wherein the capsule, after piercing, is carried into a cylindrical mixing chamber by the action of inhalation. The air arrives in this chamber through a plurality of tubes directed tangentially to the circulation periphery setting the capsule in a rotating motion and transferring the medicine from the capsule into the inhalation air. This structure is also not capable of producing sufficient centrifugal forces for the pulverization of accumulations of medicine because of the capsule's mass, rotational friction and air resistance.
British Patent No. 1472650 discloses a device for the inhalation of a powdered medicament contained in a capsule. The capsule is purged in a manner that some of the inhalation air is passed through a pierced capsule while most of the air travels past the capsule. However, piercing of the capsule is effected centrally towards the longitudinal axis of the capsule and there is no purpose to create inside the capsule a turbulent flow that would produce a major centrifugal force. Also, according to laboratory tests, the device set forth in the cited Patent (Boehringer Ingelheim) did not produce a powerful turbulence inside the capsule. Also the pulverizing effect of the device for accumulations of medicine was conventional.
British Patent No. 1118341 describes a structure for purging an open, medicine-containing container into inhalation air. As one alternative to sucking the air into a chamber containing a medicine container there is shown a structure which uses deflectors for setting the air flow in a spinning motion in the chamber. The cited Patent specification discloses that an object is to create irregular turbulence and passage of air flows against the deflectors rather than to set the air in a rotating motion as rapid as possible. Thus, the internal positioning of deflectors in the chamber severely restricts the rotating motion but creates effectively other turbulence.
Prior known are also several structures, wherein a medicament-containing capsule is pierced prior to dosage, set in its holder in a rotating motion by means of inhalation air or cut open. Prior known are also structures, wherein a medicament is transferred from a capsule into inhalation air by the application of pressurized air. Furthermore, there are known structures, wherein a powdered medicament is transferred for inhalation from a disc or a separate powdered medicament container carrying several doses of medicine. See for example, U. S. Pat. Nos. 4,046,146; 4,116,195; 4,117,844; 4,210,140 and British Patents 1,182,779; 1,396,258; 1,404,338; 1,457,352; 1,459,426; 1,502,150; 1,521,000; or Finnish Patent publication 76258, Finnish applications 863094 and 883767, and Danish publication 153631B.
None of the above cited and examined publications discloses a structure, wherein a powdered medicament would be pulverized by means of inhalation or an external gas pressure by the application of a centrifugal force resulting primarily from a powerful rotating motion with a structure described hereinafter.